Bone support of a custom triflange acetabular component over time.

Aims: To investigate the extent of bone development around the scaffold of custom triflange acetabular components (CTACs) over time. Methods: We performed a single-centre historical prospective cohort study, including all patients with revision THA using the aMace CTAC between January 2017 and March 2021. A total of 18 patients (18 CTACs) were included. Models of the hemipelvis and the scaffold component of the CTACs were created by segmentation of CT scans. The CT scans were performed immediately postoperatively and at least one year after surgery. The amount of bone in contact with the scaffold was analyzed at both times, and the difference was calculated. Results: The mean time between the implantation and the second CT scan was two years (1 to 5). The mean age of the patients during CTAC implantation was 75 years (60 to 92). The mean scaffold-bone contact area increased from 16% (SD 12.6) to 28% (SD 11.9). The mean scaffold-bone distance decreased from a mean of 6.5 mm (SD 2.0) to 5.5 mm (SD 1.6). None of the CTACs were revised or radiologically loose. Conclusion: There was a statistically significant increase of scaffold-bone contact area over time, but the total contact area of the scaffold in relation to the acetabular bone remained relatively low. As all implants remained well fixed, the question remains to what extend the scaffold contributes to the observed stability, in relation to the screws. A future design implication might be an elimination of the bulky scaffold component. This design modification would reduce production costs and may optimize the primary fit of the implant.

Deep versus moderate neuromuscular blockade during total hip arthroplasty to improve postoperative quality of recovery and immune function: protocol for a randomised controlled study.

INTRODUCTION: There is accumulating evidence that deep neuromuscular blockade (NMB) improves intraoperative surgical conditions during laparoscopic surgery. Studies investigating the effects of deep NMB in open surgery are scarce. In theory, by limiting surgical damage through deeper muscle relaxation, postoperative inflammation and concomitant immune suppression can be reduced. Therefore, this study will investigate the effects of deep NMB during total hip arthroplasty, which demands a relatively large exposure of the hip joint through and in between muscles. METHODS AND ANALYSIS: This study is a monocentre blinded randomised controlled trial in 100 patients undergoing total hip arthroplasty under general anaesthesia. Patients will be randomised in a 1:1 fashion to an intervention group of intraoperative deep NMB (a post-tetanic count of 1-2) or a control group receiving moderate NMB (a train-of-four count of 1-2). NMB will be achieved by continuous or bolus administration of rocuronium, respectively. The primary endpoint is the quality of recovery at postoperative day 1 measured by the Quality of Recovery-40 Questionnaire, analysed by Analysis of Variance. The secondary endpoint is postoperative innate immune function, measured by ex vivo production capacity of tumour necrosis factor and interleukin-1ß on endotoxin stimulation of whole blood. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee 'METC Oost-Nederland' (reference number 2022-15754). Informed consent will be obtained prior to study participation. Study results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT05562999) and EudraCT Registry (2022-002451-19).

[Decision making in frail patients with a hip fracture]. / Besluitvorming bij kwetsbare patiënt met heupfractuur.

BACKGROUND: When an older patient presents herself at the emergency department with a femur fracture different doctors are involved: the geriatrician, the orthopaedic or trauma- surgeon and the anaesthesiologist. Together they form an ad hoc team and are in charge of organising the best medical care for the patient. CASE DESCRIPTION: In this case description we present a patient with cardiovascular comorbidity and dementia. Mis-interpretation or missing information can lead to different treatment decisions and outcomes. CONCLUSION: Effective cooperation and transfer of information in physical consultation is crucial in the care of frail patients.

Thirty years of experience with instrumented femoral impaction bone grafting and a cemented polished Exeter stem : a prospective cohort study of 208 revision arthroplasties performed between 1991 and 2007.

AIMS: The aim of this study is to report the long-term outcomes of instrumented femoral revisions with impaction allograft bone grafting (IBG) using the X-change femoral revision system at 30 years after introduction of the technique. METHODS: We updated the outcomes of our previous study, based on 208 consecutive revisions using IBG and the X-change femoral revision system in combination with a cemented polished stem, performed in our tertiary care institute between 1991 and 2007. Kaplan-Meier survival analyses were used to determine the survival rate of the revisions with endpoint revision for any reason and aseptic loosening. Secondary outcomes were radiological loosening and patient-reported outcome measures. RESULTS: Mean age at revision total hip arthroplasty (THA) was 64.9 years (30 to 86). The most prevalent diagnosis for the femoral revision was aseptic loosening. At review in May 2021, 81 patients (85 hips) were still alive and 118 patients (120 hips; 58%) had died. Three patients (3 hips; 1%) were lost to follow-up at 11, 15, and 16 years after surgery, respectively. Data of all deceased and lost patients were included until final follow-up. The mean follow-up was 13.4 years (0 to 28). During the follow-up, 22 re-revisions were performed. The most common reason for re-revision was infection (n = 12; 54%). The survival with endpoint re-revision for any reason was 86% (95% confidence interval (CI) 79 to 91) at 20 years and 74% (95% CI 43 to 89) at 25 years after surgery. The survival for endpoint re-revision for aseptic loosening was 97% (95% CI 91 to 99) after both 20 and 25 years. CONCLUSION: We conclude that femoral IBG is a valuable technique that can reconstitute femoral bone loss in the long term. After 25 years of follow-up, few re-revisions for aseptic loosening were required. Also, the overall revision rate is very acceptable at a long follow-up. This technique is especially attractive for younger patients facing femoral revisions with extensive bone loss.Cite this article: Bone Joint J 2022;104-B(9):1039-1046.

Dual-contrast computed tomography enables detection of equine posttraumatic osteoarthritis in vitro.

To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual-energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potential of QDECT to evaluate tissue quality surrounding cartilage lesions in an equine model, hypothesizing that QDECT allows detection of posttraumatic degeneration by providing quantitative information on PG and water contents based on the partitions of cationic and nonionic agents in a contrast mixture. Posttraumatic osteoarthritic samples were obtained from a cartilage repair study in which full-thickness chondral defects were created surgically in both stifles of seven Shetland ponies. Control samples were collected from three nonoperated ponies. The experimental (n = 14) and control samples (n = 6) were immersed in the contrast agent mixture and the distributions of the agents were determined at various diffusion time points. As a reference, equilibrium moduli, dynamic moduli, and PG content were measured. Significant differences (p < 0.05) in partitions between the experimental and control samples were demonstrated with cationic contrast agent at 30 min, 60 min, and 20 h, and with non-ionic agent at 60 and 120 min. Significant Spearman's rank correlations were obtained at 20 and 24 h (ρ = 0.482-0.693) between the partition of cationic contrast agent, cartilage biomechanical properties, and PG content. QDECT enables evaluation of posttraumatic changes surrounding a lesion and quantification of PG content, thus advancing the diagnostics of the extent and severity of cartilage injuries.

[Arthroscopy for degenerative meniscal tears: from standard to exception]. / Artroscopie voor degeneratief meniscusletsel.

Osteoarthritis of the knee is often accompanied by degeneration of the meniscus. Worldwide, the arthroscopic partial meniscectomy has been a standard of care for patients with knee pain in the presence a degenerative meniscal tear. However, in recent years, clinical studies have proven that a meniscectomy is not effective in the osteoarthritic knee. Physiotherapy is often as effective. The updated Dutch guidelines for meniscal tears therefore recommend an arthroscopic partial meniscectomy or fixation in case of a locked knee and for traumatic meniscal tears in younger patients. There also is an indication for a meniscectomy after failure of conservative treatment in case of a symptomatic meniscal tear in the absence of osteoarthritis.

Evaluation of articular cartilage with quantitative MRI in an equine model of post-traumatic osteoarthritis.

Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post-traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age-matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included T1 , T2 , continuous-wave T1ρ (CWT1ρ ), adiabatic T1ρ (AdT1ρ ), and T2ρ (AdT2ρ ) and relaxation along a fictitious field (TRAFF ). For reference, cartilage equilibrium and dynamic moduli, proteoglycan content and collagen fiber orientation were determined. Mean values and profiles from full-thickness cartilage regions of interest, at increasing distances from the lesions, were used to compare experimental against control and to correlate qMRI with the references. Significant alterations were detected by qMRI parameters, including prolonged T1 , CWT1ρ , and AdT1ρ in the regions adjacent to the lesions. The changes were confirmed by the reference methods. CWT1ρ was more strongly associated with the reference measurements and prolonged in the affected regions at lower spin-locking amplitudes. Moderate to strong correlations were found between all qMRI parameters and the reference parameters (ρ = -0.531 to -0.757). T1 , low spin-lock amplitude CWT1ρ , and AdT1ρ were most responsive to changes in visually intact cartilage adjacent to the lesions. In the context of PTOA, these findings highlight the potential of T1 , CWT1ρ , and AdT1ρ in evaluation of compositional and structural changes in cartilage.

[Applications of 3D printing in medicine; 5 years later]. / Mogelijkheden van 3D-printen in de geneeskunde.

5 years ago, we described the emergence of 3D printing in medicine. It was about 3D printing of anatomical structures, patient-specific drilling guides, cutting templates and implants and printing of living cells, growth factors and biomaterials ('bioprinting'). Surgeons are increasingly making use of 3D printing possibilities in preparation of surgeries on patients with complicated anatomies. Using tangible 3D models, it is easier for surgeons to prepare for surgeries and discussions with patients. They can also use 3D models as a tool to help with the training of young surgeons. Permanent titanium implants are increasingly being printed. Bioprinting is still in its infancy and there are no direct clinical applications yet. As we already predicted 5 years ago, many hurdles still have to be taken before broad clinical application of bioprinted products will become a reality.

Arthroscopic Determination of Cartilage Proteoglycan Content and Collagen Network Structure with Near-Infrared Spectroscopy.

Conventional arthroscopic evaluation of articular cartilage is subjective and insufficient for assessing early compositional and structural changes during the progression of post-traumatic osteoarthritis. Therefore, in this study, arthroscopic near-infrared (NIR) spectroscopy is introduced, for the first time, for in vivo evaluation of articular cartilage thickness, proteoglycan (PG) content, and collagen orientation angle. NIR spectra were acquired in vivo and in vitro from equine cartilage adjacent to experimental cartilage repair sites. As reference, digital densitometry and polarized light microscopy were used to evaluate superficial and full-thickness PG content and collagen orientation angle. To relate NIR spectra and cartilage properties, ensemble neural networks, each with two different architectures, were trained and evaluated by using Spearman's correlation analysis (ρ). The ensemble networks enabled accurate predictions for full-thickness reference properties (PG content: ρin vitro, Val= 0.691, ρin vivo= 0.676; collagen orientation angle: ρin vitro, Val= 0.626, ρin vivo= 0.574) from NIR spectral data. In addition, the networks enabled reliable prediction of PG content in superficial (25%) cartilage (ρin vitro, Val= 0.650, ρin vivo= 0.613) and cartilage thickness (ρin vitro, Val= 0.797, ρin vivo= 0.596). To conclude, NIR spectroscopy could enhance the detection of initial cartilage degeneration and thus enable demarcation of the boundary between healthy and compromised cartilage tissue during arthroscopic surgery.

Arthroscopic near infrared spectroscopy enables simultaneous quantitative evaluation of articular cartilage and subchondral bone in vivo.

Arthroscopic assessment of articular tissues is highly subjective and poorly reproducible. To ensure optimal patient care, quantitative techniques (e.g., near infrared spectroscopy (NIRS)) could substantially enhance arthroscopic diagnosis of initial signs of post-traumatic osteoarthritis (PTOA). Here, we demonstrate, for the first time, the potential of arthroscopic NIRS to simultaneously monitor progressive degeneration of cartilage and subchondral bone in vivo in Shetland ponies undergoing different experimental cartilage repair procedures. Osteochondral tissues adjacent to the repair sites were evaluated using an arthroscopic NIRS probe and significant (p < 0.05) degenerative changes were observed in the tissue properties when compared with tissues from healthy joints. Artificial neural networks (ANN) enabled reliable (ρ = 0.63-0.87, NMRSE = 8.5-17.2%, RPIQ = 1.93-3.03) estimation of articular cartilage biomechanical properties, subchondral bone plate thickness and bone mineral density (BMD), and subchondral trabecular bone thickness, bone volume fraction (BV), BMD, and structure model index (SMI) from in vitro spectral data. The trained ANNs also reliably predicted the properties of an independent in vitro test group (ρ = 0.54-0.91, NMRSE = 5.9-17.6%, RPIQ = 1.68-3.36). However, predictions based on arthroscopic NIR spectra were less reliable (ρ = 0.27-0.74, NMRSE = 14.5-24.0%, RPIQ = 1.35-1.70), possibly due to errors introduced during arthroscopic spectral acquisition. Adaptation of NIRS could address the limitations of conventional arthroscopy through quantitative assessment of lesion severity and extent, thereby enhancing detection of initial signs of PTOA. This would be of high clinical significance, for example, when conducting orthopaedic repair surgeries.

Low sensitivity of a-defensin (Synovasure) test for intra-operative exclusion of prosthetic joint infection.

Background and purpose - The Synovasure lateral flow test was developed as a rapid test for the detection or exclusion of periprosthetic joint infection (PJI). 3 studies have reported promising results on its diagnostic value in total joint revision surgery. We aimed to assess the sensitivity and specificity of the Synovasure test to exclude infection in patients undergoing revision surgery for suspected early aseptic loosening of a total hip or knee arthroplasty. Patients and methods - In a prospective study design, 37 patients who underwent revision surgery for suspected early aseptic loosening (< 3 years after primary arthroplasty) were included. The Synovasure test was used intraoperatively to confirm the aseptic nature of the loosening and 6 tissue cultures were obtained in all cases. Exclusion criteria were patients with a preoperatively confirmed PJI, acute revisions (< 90 days after primary arthroplasty) and cases with malpositioning, wear, or instability of the prosthesis. Results - 5 of the 37 patients were diagnosed with a PJI based on the intraoperative tissue cultures. In only 1 out of these 5 cases this was confirmed by the intraoperative Synovasure test. No tests were falsely positive. Interpretation - In this case series the Synovasure lateral flow test had a low sensitivity to exclude PJI in patients with suspected aseptic loosening. The role of the Synovasure lateral flow test in the intraoperative exclusion of PJI during revision surgery for suspected early aseptic loosening appears to be more limited than previously indicated.

Yield stress determines bioprintability of hydrogels based on gelatin-methacryloyl and gellan gum for cartilage bioprinting.

Bioprinting of chondrocyte-laden hydrogels facilitates the fabrication of constructs with controlled organization and shape e.g. for articular cartilage implants. Gelatin-methacryloyl (gelMA) supplemented with gellan gum is a promising bio-ink. However, the rheological properties governing the printing process, and the influence of gellan gum on the mechanical properties and chondrogenesis of the blend, are still unknown. Here, we investigated the suitability of gelMA/gellan for cartilage bioprinting. Multiple concentrations, ranging from 3% to 20% gelMA with 0%-1.5% gellan gum, were evaluated for their printability, defined as the ability to form filaments and to incorporate cells at 15 °C-37 °C. To support the printability assessment, yield stress and viscosity of the hydrogels were measured. Stiffness of UV-cured constructs, as well as cartilage-like tissue formation by embedded chondrocytes, were determined in vitro. A large range of gelMA/gellan concentrations were printable with inclusion of cells and formed the bioprinting window. The addition of gellan gum improved filament deposition by inducing yielding behavior, increased construct stiffness and supported chondrogenesis. High gellan gum concentrations, however, did compromise cartilage matrix production and distribution, and even higher concentrations resulted in too high yield stresses to allow cell encapsulation. This study demonstrates the high potential of gelMA/gellan blends for cartilage bioprinting and identifies yield stress as a dominant factor for bioprintability.

Thermogelling and Chemoselectively Cross-Linked Hydrogels with Controlled Mechanical Properties and Degradation Behavior.

Chemoselectively cross-linked hydrogels have recently gained increasing attention for the development of novel, injectable biomaterials given their limited side reactions. In this study, we compared the properties of hydrogels obtained by native chemical ligation (NCL) and its recently described variation termed oxo-ester-mediated native chemical ligation (OMNCL) in combination with temperature-induced physical gelation. Triblock copolymers consisting of cysteine functionalities, thermoresponsive N-isopropylacrylamide (NIPAAm) units and degradable moieties were mixed with functionalized poly(ethylene glycol) (PEG) cross-linkers. Thioester or N-hydroxysuccinimide (NHS) functionalities attached to PEG reacted with cysteine residues of the triblock copolymers via either an NCL or OMNCL pathway. The combined physical and chemical cross-linking resulted in rapid network formation and mechanically strong hydrogels. Stiffness of the hydrogels was highest for thermogels that were covalently linked via OMNCL. Specifically, the storage modulus after 4 h reached a value of 26 kPa, which was over a 100 times higher than hydrogels formed by solely thermal physical interactions. Endothelial cells showed high cell viability of 98 ± 2% in the presence of OMNCL cross-linked hydrogels after 16 h of incubation, in contrast to a low cell viability (13 ± 7%) for hydrogels obtained by NCL cross-linking. Lysozyme was loaded in the gels and after 2 days more than 90% was released, indicating that the cross-linking reaction was indeed chemoselective as the protein was not covalently grafted to the hydrogel network. Moreover, the degradation rates of these hydrogels under physiological conditions could be tailored from 12 days up to 6 months by incorporation of a monomer containing a hydrolyzable lactone ring in the thermosensitive triblock copolymer. These results demonstrate a high tunability of mechanical properties and degradation rates of these in situ forming hydrogels that could be used for a variety of biomedical applications.

Reinforcement of hydrogels using three-dimensionally printed microfibres.

Despite intensive research, hydrogels currently available for tissue repair in the musculoskeletal system are unable to meet the mechanical, as well as the biological, requirements for successful outcomes. Here we reinforce soft hydrogels with highly organized, high-porosity microfibre networks that are 3D-printed with a technique termed as melt electrospinning writing. We show that the stiffness of the gel/scaffold composites increases synergistically (up to 54-fold), compared with hydrogels or microfibre scaffolds alone. Modelling affirms that reinforcement with defined microscale structures is applicable to numerous hydrogels. The stiffness and elasticity of the composites approach that of articular cartilage tissue. Human chondrocytes embedded in the composites are viable, retain their round morphology and are responsive to an in vitro physiological loading regime in terms of gene expression and matrix production. The current approach of reinforcing hydrogels with 3D-printed microfibres offers a fundament for producing tissue constructs with biological and mechanical compatibility.

Crosslinkable hydrogels derived from cartilage, meniscus, and tendon tissue.

Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found their way to clinical applications, their use in the engineering of cartilage tissue has only been explored to a limited extent. We set out to generate hydrogels from several tissue-derived matrices, as hydrogels are the current preferred cell carriers for cartilage repair. Equine cartilage, meniscus, and tendon tissue was harvested, decellularized, enzymatically digested, and functionalized with methacrylamide groups. After photo-cross-linking, these tissue digests were mechanically characterized. Next, gelatin methacrylamide (GelMA) hydrogel was functionalized with these methacrylated tissue digests. Equine chondrocytes and mesenchymal stromal cells (MSCs) (both from three donors) were encapsulated and cultured in vitro up to 6 weeks. Gene expression (COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14), cartilage-specific matrix formation, and hydrogel stiffness were analyzed after culture. The cartilage, meniscus, and tendon digests were successfully photo-cross-linked into hydrogels. The addition of the tissue-derived matrices to GelMA affected chondrogenic differentiation of MSCs, although no consequent improvement was demonstrated. For chondrocytes, the tissue-derived matrix gels performed worse compared to GelMA alone. This work demonstrates for the first time that native tissues can be processed into crosslinkable hydrogels for the engineering of tissues. Moreover, the differentiation of encapsulated cells can be influenced in these stable, decellularized matrix hydrogels.

Biofabrication of reinforced 3D-scaffolds using two-component hydrogels.

Progress in biofabrication technologies is mainly hampered by the limited number of suitable hydrogels that can act as bioinks. Here, we present a new bioink for 3D-printing, capable of forming large, highly defined constructs. Hydrogel formulations consisted of a thermoresponsive polymer mixed with a poly(ethylene glycol) (PEG) or a hyaluronic acid (HA) cross-linker with a total polymer concentration of 11.3 and 9.1 wt% respectively. These polymer solutions were partially cross-linked before plotting by a chemoselective reaction called oxo-ester mediated native chemical ligation, yielding printable formulations. Deposition on a heated plate of 37 °C resulted in the stabilization of the construct due to the thermosensitive nature of the hydrogel. Subsequently, further chemical cross-linking of the hydrogel precursors proceeded after extrusion to form mechanically stable hydrogels that exhibited a storage modulus of 9 kPa after 3 hours. Flow and elastic properties of the polymer solutions and hydrogels were analyzed under similar conditions to those used during the 3D-printing process. These experiments showed the ability to extrude the hydrogels, as well as their rapid recovery after applied shear forces. Hydrogels were printed in grid-like structures, hollow cones and a model representing a femoral condyle, with a porosity of 48 ± 2%. Furthermore, an N-hydroxysuccinimide functionalized thermoplastic poly-ε-caprolactone (PCL) derivative was successfully synthesized and 3D-printed. We demonstrated that covalent grafting of the developed hydrogel to the thermoplastic reinforced network resulted in improved mechanical properties and yielded high construct integrity. Reinforced constructs also containing hyaluronic acid showed high cell viability of chondrocytes, underlining their potential for further use in regenerative medicine applications.

Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles.

The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 ± 2.5% vs. 39.5 ± 8.3% (mean ± standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel.

Decellularized cartilage-derived matrix as substrate for endochondral bone regeneration.

Following an endochondral approach to bone regeneration, multipotent stromal cells (MSCs) can be cultured on a scaffold to create a cartilaginous callus that is subsequently remodeled into bone. An attractive scaffold material for cartilage regeneration that has recently regained attention is decellularized cartilage-derived matrix (CDM). Since this material has shown potential for cartilage regeneration, we hypothesized that CDM could be a potent material for endochondral bone regeneration. In addition, since decellularized matrices are known to harbor bioactive cues for tissue formation, we evaluated the need for seeded MSCs in CDM scaffolds. In this study, ectopic bone formation in rats was evaluated for CDM scaffolds seeded with human MSCs and compared with unseeded controls. The MSC-seeded samples were preconditioned in chondrogenic medium for 37 days. After 8 weeks of subcutaneous implantation, the extent of mineralization was significantly higher in the MSC-seeded constructs versus unseeded controls. The mineralized areas corresponded to bone formation with bone marrow cavities. In addition, rat-specific bone formation was confirmed by collagen type I immunohistochemistry. Finally, fluorochrome incorporation at 3 and 6 weeks revealed that the bone formation had an inwardly directed progression. Taken together, our results show that decellularized CDM is a promising biomaterial for endochondral bone regeneration when combined with MSCs at ectopic locations. Modification of current decellularization protocols may lead to enhanced functionality of CDM scaffolds, potentially offering the prospect of generation of cell-free off-the-shelf bone regenerative substitutes.

Recovery of TES-MEPs during surgical decompression of the spine: a case series of eight patients.

PURPOSE: This study aimed to illustrate the recovery of transcranial electrical stimulation motor evoked potentials during surgical decompression of the spinal cord in patients with impaired motor function preoperatively. Specific attention was paid to the duration of neurologic symptoms before surgery and the postoperative clinical recovery. METHODS: A case series of eight patients was selected from a cohort of 74 patients that underwent spine surgery. The selected patients initially had low or absent transcranial electrical stimulation motor evoked potentials followed by a significant increase after surgical decompression of the spinal cord. RESULTS: A significant intraoperative increase in amplitude of motor evoked potentials was detected after decompression of the spinal cord or cauda equina in patients suffering from spinal canal stenosis (n = 2), extradural meningioma (n = 3), or a herniated nucleus polposus (n = 3). This was related to an enhanced neurologic outcome only if patients (n = 6) had a short onset (less than ½ year) of neurologic impairment before surgery. CONCLUSIONS: In patients with a short onset of neurologic impairment because of compression of the spinal cord or caudal fibers, an intraoperative recovery of transcranial electrical stimulation motor evoked potentials can indicate an improvement of motor function postoperatively. Therefore, transcranial electrical stimulation motor evoked potentials can be considered as a useful tool to the surgeon to monitor the quality of decompression of the spinal cord.

Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs.